Cellular Mechanisms of Photoreceptor Disk Morphogenesis

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Project Summary The photoreceptor cilium is the most elaborate of all primary cilia. Its plasma membrane is extensively amplified to form a stack of disk membranes that contain a very high concentration of the visual receptor, opsin. This stack of disks forms the photoreceptor outer segment, and its organization is central to visual sensitivity and spatial resolution. The overall goal of the proposed research is to understand the cellular mechanisms involved in the morphogenesis of the disk membranes. The research plan is built on the application of molecular tools, with the use of advanced microscopy, including EM tomography and live-cell super-resolution microscopy, for high resolution, 3-D analysis. The long-term goal of the proposed research is to provide a molecular understanding of photoreceptor disk morphogenesis, including the mechanisms for delivering essential proteins to the site of membrane growth. The Specific Aims will address unknown aspects of the ciliary localization of opsin, and the roles of disk morphogenetic proteins in initiating lamellar growth, using both mouse rod photoreceptors in vivo and cultures of cells bearing unspecialized cilia. Our findings will provide understanding of a key area of photoreceptor cell biology. They will also be fundamental to our understanding of the pathogenesis of retinal disease that ensues from perturbations of disk membrane morphogenesis.